Design and construction of light-regulated gene transcription and protein translation systems in yeast p. Pastoris.

INTRODUCTION: P. pastoris is a common host for effective biosynthesis of heterologous proteins as well as small molecules. Accurate regulation of gene transcription and protein synthesis is necessary to coordinate synthetic gene circuits and optimize cellular energy distribution. Traditional methanol or other inducible promoters, natural or engineered, have defects in either fermentation safety or expression capacity. The utilization of chemical inducers typically adds complexity to the product purification process, but there is no other well-controlled protein synthesis system than promoters yet. OBJECTIVE: The study aimed to address the aforementioned challenges by constructing light-regulated gene transcription and protein translation systems with excellent expression capacity and light sensitivity. METHODS: Trans-acting factors were designed by linking the N. crassa blue-light sensor WC-1 with the activation domain of endogenous transcription factors. Light inducible or repressive promoters were then constructed through chimeric design of cis-elements (light-responsive elements, LREs) and endogenous promoters. Various configurations of trans-acting factor/LRE pairs, along with different LRE positions and copy numbers were tested for optimal promoter performance. In addition to transcription, a light-repressive translation system was constructed through the "rare codon brake" design. Rare codons were deliberately utilized to serve as brakes during protein synthesis, which were switched on and off through the light-regulated changes in the expression of the corresponding pLRE-tRNA. RESULTS: As demonstrated with GFP, the light-inducible promoter 4pLRE-cPAOX1 was 70 % stronger than the constitutive promoter PGAP, with L/D ratio = 77. The light-repressive promoter PGAP-pLRE was strictly suppressed by light, with expression capacity comparable with PGAP in darkness. As for the light-repressive translation system, the "triple brake" design successfully eliminated leakage and achieved light repression on protein synthesis without any impact on mRNA expression. CONCLUSION: The newly designed light-regulated transcription and translation systems offer innovative tools that optimize the application of P. pastoris in biotechnology and synthetic biology.

Targeting post-stroke neuroinflammation with Salvianolic acid A: molecular mechanisms and preclinical evidence.

Salvianolic acid A (SalA), a bioactive compound extracted from Salvia miltiorrhiza, has garnered considerable interest for its potential in ameliorating the post-stroke neuroinflammation. This review delineates the possible molecular underpinnings of anti-inflammatory and neuroprotective roles of SalA, offering a comprehensive analysis of its therapeutic efficacy in preclinical studies of ischemic stroke. We explore the intricate interplay between post-stroke neuroinflammation and the modulatory effects of SalA on pro-inflammatory cytokines, inflammatory signaling pathways, the peripheral immune cell infiltration through blood-brain barrier disruption, and endothelial cell function. The pharmacokinetic profiles of SalA in the context of stroke, characterized by enhanced cerebral penetration post-ischemia, makes it particularly suitable as a therapeutic agent. Preliminary clinical findings have demonstrated that salvianolic acids (SA) has a positive impact on cerebral perfusion and neurological deficits in stroke patients, warranting further investigation. This review emphasizes SalA as a potential anti-inflammatory agent for the advancement of innovative therapeutic approaches in the treatment of ischemic stroke.

Guided Cooperation in Hierarchical Reinforcement Learning via Model-Based Rollout.

Goal-conditioned hierarchical reinforcement learning (HRL) presents a promising approach for enabling effective exploration in complex, long-horizon reinforcement learning (RL) tasks through temporal abstraction. Empirically, heightened interlevel communication and coordination can induce more stable and robust policy improvement in hierarchical systems. Yet, most existing goal-conditioned HRL algorithms have primarily focused on the subgoal discovery, neglecting interlevel cooperation. Here, we propose a novel goal-conditioned HRL framework named Guided Cooperation via Model-Based Rollout (GCMR; code is available at https://github.com/HaoranWang-TJ/GCMR_ACLG_official), aiming to bridge interlayer information synchronization and cooperation by exploiting forward dynamics. First, the GCMR mitigates the state-transition error within off-policy correction via model-based rollout, thereby enhancing sample efficiency. Second, to prevent disruption by the unseen subgoals and states, lower level Q -function gradients are constrained using a gradient penalty with a model-inferred upper bound, leading to a more stable behavioral policy conducive to effective exploration. Third, we propose a one-step rollout-based planning, using higher level critics to guide the lower level policy. Specifically, we estimate the value of future states of the lower level policy using the higher level critic function, thereby transmitting global task information downward to avoid local pitfalls. These three critical components in GCMR are expected to facilitate interlevel cooperation significantly. Experimental results demonstrate that incorporating the proposed GCMR framework with a disentangled variant of hierarchical reinforcement learning guided by landmarks (HIGL), namely, adjacency constraint and landmark-guided planning (ACLG), yields more stable and robust policy improvement compared with various baselines and significantly outperforms previous state-of-the-art (SOTA) algorithms.

Bulk-RNA and single-nuclei RNA seq analyses reveal the role of lactate metabolism-related genes in Alzheimer's disease.

Dysfunctional lactate metabolism in the brain has been implicated in neuroinflammation, Aß deposition, and cell disturbance, all of which play a significant role in the pathogenesis of Alzheimer's disease (AD). In this study, we aimed to investigate the lactate metabolism-related genes (LMRGs) in AD via an integrated bulk RNA and single-nuclei RNA sequencing (snRNA-seq) analysis, with a specific focus on microglia. We obtained 26 HC and 24 AD snRNA-seq samples originated from human prefrontal cortex in Gene Expression Omnibus (GEO) database and collected 873 LMRGs from three databases, namely MSigDB, The Human Protein Atlas and GeneCards. Bulk RNA was analyzed with LMRG characteristics in AD by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), the protein-protein interaction (PPI), CytoHubba-MCC, Support Vector Machine (SVM) algorithms analyses. Then we conducted the Receiver Operating Characteristic (ROC) curve, correlation, and connection network analyses for biomarkers. Their differential expression validation was performed using AlzData database. The single-nuclei RNA analysis of microglia was applied to identify hub genes and pathways using cell-cell communication analysis and high dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Support Vector Machine (SVM) algorithm showed an AUC of 0.967, a sensitivity of 93.30% and a specificity of 100.00%. Our analysis identified biomarkers with LMRG characteristics, namely INSR, CDKL1, and PNISR. ROC analysis revealed that each of these biomarkers exhibited excellent diagnostic potential, as evidenced by their respective area under the curve (AUC) values: INSR (AUC: 0.679), CDKL1 (AUC: 0.788), and PNISR (AUC: 0.724). Correlation analysis showed that biomarkers exhibited a positive correlation with each other. Connection network illustrated their shared biological processes: aging, phosphorylation, metabolic process, and apoptosis. Cell-cell communication analysis revealed that GALECTIN signaling pathway was exclusively expressed in AD microglia, and only LGALS9 exhibited significant overexpression. HdWGCNA identified FTH1 as a hub gene enriched in ferroptosis and mineral absorption pathways within microglia. The roles of INSR, CDKL1, PNISR, LGALS9, and FTH1 should be taken into account to enhance our understanding of lactate metabolism in the context of AD.

Quantitative assessment of intertarget position variations based on 4D-CT and 4D-CBCT simulations in single-isocenter multitarget lung stereotactic body radiation therapy.

BACKGROUND: In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it. METHODS: We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors. RESULTS: The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk. CONCLUSIONS: This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.

Development of a live attenuated vaccine candidate for equid alphaherpesvirus 1 control: a step towards efficient protection.

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the ΔgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the ΔUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the ΔUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection.

VNN1 Gene Expression and Polymorphisms Associated with Chicken Carcass Traits.

This study aimed to investigate the association between hepatic VNN1 expression and carcass traits in Mahuang chickens as well as to identify polymorphisms in the upstream and downstream regions of VNN1 that could potentially be associated with these carcass traits. The study revealed that VNN1 expression levels in liver correlated with various carcass traits such as dressed weight, eviscerated weight, and abdominal fat weight. A total of 39 polymorphic sites were identified, among which 23 were found to be associated with 15 different carcass traits. These polymorphic sites were organized into three distinct haplotype blocks, with BLOCK2 and BLOCK3 being associated with various eviscerated weight percentages, thigh weight, breast muscle weight, wing weight, and other traits. The study underscores the significant role of VNN1 in influencing the carcass traits of Mahuang chickens and sheds light on the genetic foundations of these traits. The findings provide valuable insights that could inform breeding strategies aimed at optimizing traits relevant to market demands and slaughtering efficiency.

Wearable and Multiplexed Biosensors based on Oxide Field-Effect Transistors.

Wearable sensors designed for continuous, non-invasive monitoring of physicochemical signals are important for portable healthcare. Oxide field-effect transistor (FET)-type biosensors provide high sensitivity and scalability. However, they face challenges in mechanical flexibility, multiplexed sensing of different modules, and the absence of integrated on-site signal processing and wireless transmission functionalities for wearable sensing. In this work, a fully integrated wearable oxide FET-based biosensor array is developed to facilitate the multiplexed and simultaneous measurement of ion concentrations (H+, Na+, K+) and temperature. The FET-sensor array is achieved by utilizing a solution-processed ultrathin (≈6 nm thick) In2O3 active channel layer, exhibiting high compatibility with standard semiconductor technology, good mechanical flexibility, high uniformity, and low operational voltage of 0.005 V. This work provides an effective method to enable oxide FET-based biosensors for the fusion of multiplexed physicochemical information and wearable health monitoring applications.

Equality of healthcare resource allocation between impoverished counties and non-impoverished counties in Northwest China: a longitudinal study.

BACKGROUND: The Health and Medical Assistance Program for Poverty Alleviation is part of China's targeted poverty elimination strategy, which aims to protect poor people's right to health and prevent them from becoming trapped in or returning to poverty because of illness. Many tasks have been defined in this program, including raising the medical insurance level, providing a triage system, improving medical and health services, and enhancing people's health. One pivotal aspect of this initiative involves equitable health resource allocation, a key measure aimed at bolstering medical and health services. This study aimed to analyze and compare health resource allocations in different counties in Northwest China after the implementation of the program. METHODS: The Gini coefficient quantifies the level of distributional equality, the Theil index assesses the sources of inequality, and the Health Resource Agglomeration Degree gauges the accessibility of health resources. RESULTS: 1) The health resource allocation distributed based on population(Gini Coefficient < 0.45) was more equitable than that distributed based on area(Gini Coefficient > 0.35) among counties in Northwest China. 2) The contribution rate within non-impoverished counties is higher than that of impoverished counties, which means the inequality within non-impoverished counties. 3) The allocation of beds in medical institutions by area in non-impoverished counties was better than that in impoverished counties, and accessibility to health services for residents in non-impoverished counties was better than that in impoverished counties. CONCLUSION: The analysis of health resource allocation among the five provinces in Northwest China revealed significant differences in equality among the five provinces in Northwest China, and the differences were mainly derived from the non-impoverished counties. Although the equality is gradually improving, the number of health resources in impoverished counties remain lower than that in non-impoverished counties.Subsequently, it is essential to ensure equitable distribution of healthcare resources while also taking into account their utilization and quality.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

A novel fluorescent and photothermal probe based on nanozyme-mediated cascade reaction for detecting organophosphorus pesticide residues.

In this study, a nanozyme (ZIF-Co-Cys) with high oxidase-like catalytic activity was prepared, and a ratiometric fluorescent/photothermal dual-mode probe was constructed for organophosphorus pesticides (OPs) detection based on the competitive effect of ZIF-Co-Cys and the enzymatic reaction product of acid phosphatase (ACP) on o-phenylenediamine and the inhibition effect of OPs on ACP activity. Using dimethyl dichloroviny phosphate (DDVP) as the model, both the fluorescence intensity ratio and the temperature change of the probe solution exhibited an excellent correlation with OPs concentration. The detection limits were 1.64 ng/mL and 0.084 ng/mL, respectively. Additionally, the detection of DDVP residues in real samples verified the outstanding anti-interference and accuracy of the probe. This work not only provided a complementary dual-mode method for the accurate and rapid detection of OPs residues in complex samples, but also supplied a new insight into the design of a multi-mode sensing platform based on the cascade reaction of nanozyme.

Clinical characteristics and treatment of Marjolin's ulcer at a major burn center in northwest China: a retrospective review of 126 cases.

OBJECTIVE: Marjolin's ulcer (MU) is a rare, aggressive skin tumor. There are numerous case reports but large long-term studies are lacking, necessitating further exploration of its treatment. This study aimed to summarize and analyze the characteristics, treatment methods, and prognosis of MU. METHODS: We retrospectively analyzed the clinical data of 126 patients with MU, treated between January 2013 and January 2023 at the burn center. Demographic data, clinical characteristics, treatment, and prognosis were statistically analyzed. RESULTS: Of the 126 included patients, 104 were followed up for 0.1-10.2 years. The most common cause of the primary injury was flame burn (50.8%). Lesions were commonly observed on the lower limbs (47.6%). The predominant histopathological type was squamous cell carcinoma (92.8%). Among the 126 patients, 35 (27.8%) presented with bone invasion, 37 (29.4%) presented with enlarged lymph nodes, and 9 (7.1%) had lymph node metastasis. Extensive local excision (83.3%) was the most common surgical procedure; the defect was repaired using skin grafting (41.9%), free flaps (37.1%), and local flaps (21.0%). Multivariate analysis revealed that bone invasion and lymph node involvement were risk factors for postoperative recurrence. Survival analysis showed that age, latency period, pathological type, and recurrence were significant risk factors for survival. CONCLUSIONS: Extensive local resection is necessary to eradicate tumors, and patient follow-up should be more frequent within 1 year postoperatively. As MU is preventable, it is essential to reach a quick diagnosis and avoid delayed management before the occurrence of deadly metastases.

The vacated space of volume/price of the drugs centralized procurement with quantity in secondary and above public hospitals of China.

BACKGROUND: In 2018, the National Centralized Drug Procurement (NCDP) policy has been implemented in 11 provinces, and promoted across the country in 2019. The main feature of the policy is "volume for price", therefore, it is necessary to measure the price relationship, not only to reduce the price of drugs, reduce the burden of patients' medical costs, but also facilitate pharmaceutical companies to access enough innovation incentives. The aim of this study was to assess the vacated space effect of the drug centralized procurement by national organizations in exchange of price for quantity. METHODS: A difference-in-differences (DID) model was employed to analyze the effect of the 4 + 7 pilot drugs centralized purchasing policy on drug sales volume and selected versus clinically substitutable unselected varieties, using observational data from 2018 to 2019. We compared drug procurement data between secondary and above public hospitals in pilot and non-pilot cities throughout China. RESULTS: The study showed that the average treatment effect (ATE) of sales in the in-hospital market for the selected supply varieties in centralized purchasing is -0.42, and with a sales volume of 0.49. This indicates a volume-price vacated space of 1.16 ~ 1.17 DDD (defined daily dose)/Yuan, implying that for every 1 defined daily dose (DDD) increase in reported volume, the standardized price decreased by 1.16-1.17 Yuan. The ATE of in-hospital market sales for drugs not selected in centralized procurement shows a decrease of 0.13. This finding highlights the presence of the price linkage effect. The ATE of sales volume is 0.57, indicating a volume-price space of 4.38 ~ 4.39 DDD/Yuan for unselected drugs, approximately 3.75 higher relative to that of the selected ones. CONCLUSIONS: The ratio of the volume-price space of clinically substitutable unselected and selected drugs may serve as direct evidence for evaluating the shift from centralized purchasing of drug varieties to clinically substitutable other ones. To strengthen the volume-based negotiation approach and maximize the effectiveness of centralized purchasing policies, we recommend the strategic implementation of a three-tiered centralized purchasing system, the expansion of drug coverage, and the introduction of relevant constraints and incentives.

Distinct multitrophic biodiversity composition and community organization in a freshwater lake and a hypersaline lake on the Tibetan Plateau.

Alpine lakes play pivotal roles in plateau hydrological processes but are highly sensitive to climate change, yet we lack comprehensive knowledge of their multitrophic biodiversity patterns. Here, we compared the biodiversity characteristics of diverse taxonomic groups across water depths and in surface sediments from a freshwater lake and a hypersaline lake on the northwestern Tibetan Plateau. Using multi-marker environmental DNA metabarcoding, we detected 134 cyanobacteria, 443 diatom, 1,519 invertebrate, and 28 vertebrate taxa. Each group had a substantially different community composition in the two lakes, and differences were also found between water and sediments within each lake. Cooccurrence network analysis revealed higher network complexity, lower modularity, and fewer negative cohesions in the hypersaline lake, suggesting that high salinity may destabilize ecological networks. Our results provide the first holistic view of Tibetan lake biodiversity under contrasting salinity levels and reveal structural differences in the ecological networks that may impact ecosystem resilience.

Amphiphilic Polymer Electrolyte Blocking Lattice Oxygen Evolution from High-Voltage Nickel-rich Cathodes for Ultra-Thermal Stabile Batteries.

Ni-rich cathodes have been intensively adopted in Li-ion batteries to pursuit high energy density, which still suffering irreversible degradation at high voltage. Some unstable lattice O2- species in Ni-rich cathodes would be oxidized to singlet oxygen 1O2 and released at high volt, which lead to irreversible phase transfer from the layered rhombohedral (R) phase to a spinel-like (S) phase. To overcome the issue, the amphiphilic copolymers (UMA-Fx) electrolyte were prepared by linking hydrophobic C-F side chains with hydrophilic subunits, which could self-assemble on Ni-rich cathode surface and convert to stable cathode-electrolyte interphase layer. Thereafter, the oxygen releasing of polymer coated cathode was obviously depressed and substituted by the Co oxidation (Co3+→Co4+) at high volt (>4.2 V), which could suppressed irreversible phase transfer and improve cycling stability. Moreover, the amphiphilic polymer electrolyte was also stable with Li anode and had high ion conductivity. Therefore, the NCM811//UMA-F6//Li pouch cell exhibited outstanding energy density (362.97 Wh/kg) and durability (cycled 200 times at 4.7 V), which could be stalely cycled even at 120°C without short circuits or explosions.

Strong, tough, conductive and transparent nanocellulose hydrogel based on Ca2+-induced cross-linked double-networks and its adsorption of methylene blue dye.

A novel multi-performance SHNC/SA/CaCl2 hydrogel with multi-performance was prepared via ultra-low-temperature freeze-thaw cycling and Ca2+ cross-linking for the removal of methylene blue (MB) from industrial wastewater. Various methods were used to characterize the structure and properties of hydrogel, and the internal structure of hydrogel showed a three-dimensional network with hydrogen and ester bonds. The SHNC/SA/CaCl2-15 hydrogel exhibited the highest tensile properties (elongation = 800 %), viscoelasticity (90 kPa), compressive strength (0.45 MPa), tensile strength (0.47 MPa) and ionic conductivity (4.34 S/cm). The maximum adsorption capacity of 2 g SHNC/SA/CaCl2-15 hydrogel was 608.49 mg/g at 40 °C, pH = 8 and adsorption 24 h. The adsorption process of hydrogel toward MB was more consistent with the second-order kinetic model and Langmuir isothermal adsorption model. According to the Langmuir isotherm model, the maximum monolayer adsorption capacity of SHNC/SA/CaCl2-15 hydrogel toward MB can reach 613.88 mg/g. Finally, it was found that the removal rate of SHNC/SA/CaCl2-15 hydrogel for MB was still as high as 90 % after five cycles of the adsorption-desorption test, and it could be reused. The hydrogel can be used as cheap and reusable adsorption material for cationic dyes. Our study provides a new perspective for the development of multifunctional cellulose hydrogel adsorbent materials.

Sulfidation of Cd-Sch during the microbial sulfate reduction: Nanoscale redistribution of Cd.

Schwertmannite (Sch) is found in environments abundant in iron and sulfate. Microorganisms that utilize iron or sulfate can induce the phase transition of Schwertmannite, consequently leading to the redistribution of coexisting pollutants. However, the impact of the molar ratio of sulfate to iron (S/Fe) on the microbial-mediated transformation of Schwertmannite and its implications for the fate of cadmium (Cd) have not been elucidated. In this study, we examined how S/Fe influenced mineral transformation and the fate of Cd during microbial reduction of Cd-loaded Schwertmannite by Desulfovibrio vulgaris. Our findings revealed that an increase in the S/Fe ratio facilitated sulfate-reducing bacteria (SRB) in mitigating the toxicity of Cd, thereby expediting the generation of sulfide (S(-II)) and subsequently triggering mineral phase transformation. As the S/Fe ratio increased, the predominant minerals in the system transitioned from prismatic-cluster vivianite to rose-shaped mackinawite. The Cd phase and distribution underwent corresponding alterations. Cd primarily existed in its oxidizable state, with its distribution being directly linked not only to FeS content but also showing a robust correlation with phosphorus. The coexistence of vivianite and FeS minerals proved to be more favorable for Cd immobilization. These findings have significant implications for understanding the biogeochemistry of iron (oxyhydr)oxides and Cd fate in anaerobic environments.

In vitro generation of trophoblast like stem cells from goat pluripotent stem cells.

Since the first mouse induced pluripotent stem cells (iPSCs) was derived, the in vitro culture of domestic iPSCs functionally and molecularly comparable with mouse iPSCs has been a challenge. Here, we established dairy goat iPSCs (giPSCs) from goat ear fibroblast cells with mouse iPSCs morphology, the expression of pluripotent markers and differentiation ability in vitro delivered by piggyBac transposon with nine Dox-inducible exogenous reprogramming factors. These reprogramming factors were bOMSK (bovine OCT4, CMYC, SOX2, and KLF4), pNhL (porcine NANOG and human LIN28), hRL (human RARG and LRH1), and SV40 Large T. Notably, AF-giPSCs (induced in activin A and bFGF condition) were capable of differentiation in embryoid bodies in vitro and could contribute to interspecies chimerism in mouse E6.5 embryos in vitro, demonstrating that AF-giPSCs have the developmental capability to generate some embryonic cell lineages. Moreover, Wnt/ß-catenin signaling has an important role in driving goat induced trophoblast-like stem cells (giTLSCs) from Dox-independent giPSCs. This study will support further establishment of the stable giPSC lines without any integration of exogenous genes.

Organic fertilization co-selects genetically linked antibiotic and metal(loid) resistance genes in global soil microbiome.

Antibiotic resistance genes (ARGs) and metal(loid) resistance genes (MRGs) coexist in organic fertilized agroecosystems based on their correlations in abundance, yet evidence for the genetic linkage of ARG-MRGs co-selected by organic fertilization remains elusive. Here, an analysis of 511 global agricultural soil metagenomes reveals that organic fertilization correlates with a threefold increase in the number of diverse types of ARG-MRG-carrying contigs (AMCCs) in the microbiome (63 types) compared to non-organic fertilized soils (22 types). Metatranscriptomic data indicates increased expression of AMCCs under higher arsenic stress, with co-regulation of the ARG-MRG pairs. Organic fertilization heightens the coexistence of ARG-MRG in genomic elements through impacting soil properties and ARG and MRG abundances. Accordingly, a comprehensive global map was constructed to delineate the distribution of coexistent ARG-MRGs with virulence factors and mobile genes in metagenome-assembled genomes from agricultural lands. The map unveils a heightened relative abundance and potential pathogenicity risks (range of 4-6) for the spread of coexistent ARG-MRGs in Central North America, Eastern Europe, Western Asia, and Northeast China compared to other regions, which acquire a risk range of 1-3. Our findings highlight that organic fertilization co-selects genetically linked ARGs and MRGs in the global soil microbiome, and underscore the need to mitigate the spread of these co-resistant genes to safeguard public health.

A Study on the Growth and Physiological Toxicity Effects of the Combined Exposure of Microplastics and Cadmium on the Vicia faba L. Seedlings.

To investigate the toxicological effects of polystyrene microplastics (PS-MPs), cadmium (Cd), and their combined contamination on the growth and physiological responses of V. faba seedlings, this experiment employed a hydroponic method. The Hoagland nutrient solution served as the control, changes in root growth, physiological and biochemical indicators of V. faba seedlings under different concentrations of PS-MPs (10, 100 mg/L) alone and combined with 0.5 mg/L Cd. The results demonstrated that the root biomass, root vitality, generation rate of superoxide radicals (O2·-), malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity increased with increasing concentration under the influence of PS-MPs alone, while the soluble sugar content and peroxidase (POD) activity decreased. In the combined treatment with Cd, the trends of these indicators are generally similar to the PS-MPs alone treatment group. However, root vitality and SOD activity showed an inverse relationship with the concentration of PS-MPs. Furthermore, laser confocal and electron microscopy scanning revealed that the green fluorescent polystyrene microspheres entered the root tips of the V. faba and underwent agglomeration in the treatment group with a low concentration of PS-MPs alone and a high concentration of composite PS-MPs with Cd.